The present invention relates to a method for determination of components of urine in diapers, as well as to a method for preventing sudden infant death syndrome (i.e. cot death), which makes use of the results of such determination.
In one aspect, this prior patent application (U.S. Ser. No. 07/697,714) relates to a pharmaceutical controlled-release formulation, which comprises melatonin in combination with at least one pharmaceutical carrier, diluent or coating, which formulation releases melatonin into the plasma following administration to a human patient, according to a profile which simulates that of the normal human endogenous melatonin profile depicted in FIG. 1 of that patent application.
In another aspect, the prior patent application (U.S. Ser. No. 07/697,714) relates to a method for correcting a melatonin deficiency or distortion in the plasma melatonin level and profile in a human subject, which comprises administering to a human in which such a deficiency or distortion had been diagnosed, over a time period including at least part of the nocturnal period, an effective plasma melatonin deficiency or distortion correcting amount of melatonin in the form of a pharmaceutical controlled-release formulation defined in the preceding paragraph.
In yet another aspect, the prior patent application (U.S. Ser. No. 07/697,714) relates to a method for the prevention of sudden infant death syndrome in infants, which comprises the steps of:
(a) screening at least one infant in order to determine the plasma melatonin level(s) thereof; PA1 (b) selecting at least one infant shown in step (a) to have a deficient plasma melatonin level; and PA1 (c) administering an effective plasma melatonin deficiency correcting amount of melatonin to the at least one selected infant from step (b), the melatonin being in the form of a pharmaceutical controlled-release formulation defined above.
The entire contents of U.S. application Ser. No. 07/697,714 are incorporated herein by reference.
U.S. Pat. No. 4,600,723 discloses the administration of melatonin in order to alleviate or prevent the negative effects of disturbances in circadian rhythms of bodily performance and function, such as may occur in a change of work patterns from day to night shift, or in cases of jet lag. Although conventional oral administration is exemplified, there is mentioned the possibility of administering melatonin a slow release form to maintain high plasma levels for the whole sleep period.
U.S. Pat. No. 4,654,361 discloses the administration of melatonin order to lower intraocular pressure in a human, where such pressure is abnormally high. Conventional oral and topical routes of administration are mentioned.
U.S. Pat. No. 4,945,103 discloses a method of treating premenstrual syndrome by administering melatonin at dosage levels sufficient to alleviate the symptoms. The melatonin may be administered orally or parenterally, or in the form of an implant or suppository which will provide a sustained release of melatonin over time.
PCT Patent Application No. WO 88/07370 discloses the administration of melatonin for the purpose of inhibiting ovulation in human females, thereby effecting contraception, as well as for preventing breast cancer in women. The melatonin may be administered orally or parenterally, or in the form of an implant providing a sustained release of melatonin over time.
PCT Patent Application No. WO 89/04659 discloses the use of melatonin or related compounds, as a component in pharmaceutical compositions in order to counteract the effects of aging.
European Patent Application No. 0330625A2 discloses the production of melatonin and analogs thereof, as well as the use of melatonin administered orally, intramuscularly or endovenously for various therapeutic purposes.
The entire contents of U.S. Pat. No. 4,600,723, U.S. Pat. No. 4,654,361, U.S. Pat. No. 4,945,103, PCT Patent Application No. WO 88/07370, PCT Patent Application No. WO 89/04659 and European Patent Application No. 0330625A2, and of the U.S. issued patent equivalents, to the extent that these exist, of WO 88/07370, WO 89/04659 and EP 0330625A2, are explicitly incorporated herein by reference.
It may be noted that sudden infant death syndrome (SIDS) or cot death is a phenomenon in which an apparently healthy infant of 1-12 months of age dies suddenly, usually duping sleep. It has been shown that while body and brain weight of age-matched control and SIDS infants were not significantly different, the size of the pineal gland was significantly reduced in SIDS infants (p&lt;0.000; Sparks and Hunsaker, J. Pin. Res. 5:111 (1988), and Abstract No. 127 of the 5th Colloquium of the European Pineal Study Group, Guildford, U.K., Sep. 2, 1990). Additionally, melatonin levels in the SIDS infant blood were lower by about 50% in SIDS compared with control infants (p&lt;0.05; Wurtman and Lynch, Abstract No. 24 of the 5th Colloquium of the European Pineal Study Group, Guildford, U.K., Sep. 2, 1990). If, as seems likely from these reports, melatonin serves a critical Pole in sleep functions of the human infant, administration of melatonin to infants with a deficient melatonin level (according to the method of U.S. application Ser. No. 07/697,714, or otherwise) could prevent SIDS.
It is evidently essential to be able to readily screen infants in the age group susceptible to SIDS, in order to determine their plasma melatonin levels, and to select infants for treatment with melatonin, in order to prevent SIDS, as far as possible.
More generally, determination of urine components is often desired for diagnostic purposes. These components may be, for example, hormones and metabolites such as corticosteroids, creatinine, uric acid and catecholamines. Assays based on urine have several advantages over plasma assays, and in particular: (a) sample collection is non-invasive, (b) frequent sample collection is readily achieved, (c) hormones and metabolites accumulate in urine and thus information is not lost if some time points in a sequence have been omitted, and (d) biosafety--whereas patients' specimens and kit calibration components should be handled as if capable of transmitting infections such as hepatitis B or AIDS, these risks are lower in urine samples compared with plasma samples.
For most purposes, urine samples are collected once, usually in the morning, or accumulated for 24 hours in a reservoir, and samples of the total daily excretion are assessed. Plasma levels of most hormones, and consequently urinary levels of these hormones, and/or their metabolites, show regular diurnal fluctuations (circadian rhythms). To diagnose rhythm disturbances, these hormones need to be assessed in the blood or urine, at regular intervals over the 24 hour period, including during the night.
In infants (and in disabled or bedridden patients who do not control urine excretion), urine collection is complicated and is done by attachment to the urethral outlet of specially designed baskets. These devices are cumbersome and often become detached. Frequent sampling for assessment of circadian rhythm disturbances is almost impossible in such cases.
A very useful approach to facilitate chronobiological type diagnosis in infants (or in disabled or bedridden patients) would be to determine hormone or metabolite content in the diapers. However, such a method is limited by practical problems. A major drawback is associated with the fact that disposable diapers can absorb urine very efficiently (about 200 times their weight), but the urine cannot be recovered from the diapers, even by centrifugation. To extract materials from diapers, one needs to soak them with large volumes of water, which is not a suitable technique for mass diagnostic routines.